Laura B. Hughes, MD, MSPH has a background in rheumatology and has research skills in human genetics and biostatistics. She completed her rheumatology fellowship at the University of Alabama at Birmingham (UAB) and is a newly appointed Assistant Professor of Medicine in the Division of Clinical Immunology and Rheumatology. During her fellowship Dr. Hughes became interested in the role of genetics in susceptibility and outcomes in rheumatoid arthritis (RA). Under the mentorship of S. Louis Bridges, Jr., MD, PhD she received a Clinical Investigator Fellowship Award from the UAB GCRC and was the recipient of the UAB Walter B. Frommeyer, Jr. Fellowship in Investigative Medicine. As a fellow, Dr. Hughes focused her research on her mentor's NIH-funded project entitled, "Pharmacogenetic Markers of Methotrexate (MTX) in RA". She has presented results from this research in poster form and has 2 manuscripts in preparation. Dr. Hughes'career goals are to become a leader in research that identifies genetic predictors of drug response and toxicity in patients with RA and how these markers may vary according to race/ethnicity. Dr. Hughes has been fortunate to work with strong investigators in clinical trials, pharmacogenetic research, and statistical genetics who have given their commitment to assist in her career development. This proposal entails an educational plan that will increase her knowledge of human genetics and pharmacogenetics, as well as the technical and statistical methods required to conduct high quality patient-oriented research. The scientific project expands the scope of her previous work on genetic markers of response and toxicty to MTX by analyzing functional polymorphisms in genes encoding 2 key enzymes inhibited by MTX therapy;adenosine monophosphate deaminase-1 (AMPD1) and adenosine deaminase-1 (ADA1), in Caucasians and African-Americans with RA. This proposal will provide Dr. Hughes the necessary skills to perform high quality, innovative pharmacogenetic research that will directly impact the clinical care of patients with RA.